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Glucose Levels in Culture Medium Determine Cell Death Mode in MPP+-treated Dopaminergic Neuronal Cells

Year: 2015

Type: article

Abstract: We previously demonstrated that 1-methyl-4-phenylpyridinium (MPP(+)) causes caspase-independent, non-apoptotic death of dopaminergic (DA) neuronal cells. Here, we specifically examined whether change of glucose concentration in culture medium may play a role for determining cell death modes of DA neurons following MPP(+) treatment. By incubating MN9D cells in medium containing varying concentrations of glucose (5~35 mM), we found that cells underwent a distinct cell death as determined by morphological and biochemical criteria. At 5~10 mM glucose concentration (low glucose levels), MPP(+) induced typical of the apoptotic dell death accompanied with caspase activation and DNA fragmentation as well as cell shrinkage. In contrast, MN9D cells cultivated in medium containing more than 17.5 mM (high glucose levels) did not demonstrate any of these changes. Subsequently, we observed that MPP(+) at low glucose levels but not high glucose levels led to ROS generation and subsequent JNK activation. Therefore, MPP(+)-induced cell death only at low glucose levels was significantly ameliorated following co-treatment with ROS scavenger, caspase inhibitor or JNK inhibitor. We basically confirmed the quite similar pattern of cell death in primary cultures of DA neurons. Taken together, our results suggest that a biochemically distinct cell death mode is recruited by MPP(+) depending on extracellular glucose levels.

Source: Experimental Neurobiology

DOI: 10.5607/en.2015.24.3.197

Authors: So-Young Yoon, Young J. Oh

Institution: Yonsei University

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Ministry of Health and Welfare